CLINICAL HISTORY:

Signs and symptoms: 

Previous Treatment:  Patient was initially seen by multiple providers for “excess skin” on her right hand and left foot. Consultation at 3 years of age to Genetic and Metabolic Disorders at the Detroit Medical Center by Orthopedics was not conclusive but a diagnosis of neurofibromatosis (NF) type 1 was entertained. MRI of the left foot was performed at 3 years of age which was read as a likely venous or lymphatic structure. Follow-up with US was recommended by radiology but not performed. Patient was sent to Ophthalmology and had a normal examination.
Patient presents to our clinic, now at 6 years of age, with concerns that the masses of tissue on the left jaw, right hand, and left ankle have been proportionately growing with child’s age. She is asymptomatic and lesions do not interfere with daily life except for having to buy different sized shoes. So far, cheek and tongue lesions do not interfere with eating or swallowing and do not increase in size when illnesses are present.

Other information:  Patient was borne full-term to a then 33 year-old G2P1 who reports a normal pregnancy with no complications and no known exposures to teratogens, illegal drugs, or radiation. Patient has attained all developmental milestones and is completely age-appropriate. Parents report no behavioral problems. Patient is otherwise in good health with no known illnesses or conditions other than the soft tissue masses. Family history is non-contributory except for a maternal first cousin once removed from the patient who has been diagnosed with NF type 1.

PHYSICAL EXAM:

Left face has a prominent tumorous mass which extends into the buccal mucosal. Noted asymmetry of the left side of her tongue due to a soft-tissue mass is present. The right hypothenar eminence has a soft-tissue mass which does not seem adherent to underlying tendinous structures. The left ankle has a similar soft-tissue mass which encompasses most of the heel. No bruits or hypertrichosis are associated with the lesions. Additionally, patient has multiple café au lait spots on her legs, back, and arm. Some are larger than 5mm. No other abnormalities are noted on physical examination.

LABORATORY TESTS:

Normal Findings:
Ophthalmology and skeletal x-rays (at 3 years of age). Spinal X-ray at 3 years of age showed levoconvex curvature which was likely positional in nature.
Abnormal Findings:
Left foot MRI at 3 years of age revealed a likely venous or lymphatic structure.
MRI of hand at 6 years of age revealed a likely venous or lymphatic structure.
US performed at 6 years of age: left submandibular region and right hand are likely lymphatic malformations. Embolization was suggested as possible treatment. Left foot has a more “diffuse-type of lymphatic malformation.” MRI is suggested.

DERMATOHISTOPATHOLOGY:

Two elliptical biopsies were submitted, one from the mass on the right hand and one from the left ankle. These showed “skin with hyperkeratosis with diffuse proliferation of elongated cells in a myxoid background separated by fibrous septae. Plexiform arrangement is noted in the deep portion. No atypical changes are seen. Both lesions reach the margins of excision. No lymphatic malformation is identified.” Diagnosis is of diffuse and plexiform neurofibromas.

DIFFERENTIAL DIAGNOSIS:

1.   Proteus Syndrome
2.   Blue Rubber Bleb Nevus Syndrome
3.   Maffucci's Syndrome
4.   Isolated Venous Malformation
5.   Neurofibromatosis Type 1

SCROLL DOWN FOR ANSWER AND DISCUSSION.

CORRECT DIAGNOSIS:

Neurofibromatosis Type 1

DISCUSSION:

Our patient presented as an unusual case of NF type 1 which took greater than 3 years and multiple specialty consultations until a diagnosis was rendered. Orthopedics, Genetics, Dermatology, and Ophthalmology consultations did not result in a diagnosis or with suggestions for how to help the child’s cosmesis or possible future functional impairments. Upon initial presentation in our dermatology office the differential diagnosis represented the venous lymphatic malformations seen in Proteus or Maffucci syndromes, or possibly the enchondromas seen in Maffucci’s syndrome. Consultation with a Pediatric Dermatologist was placed. Operating under the impression that the lesions were vascular in nature due to H&P as well as past MRI and recent US evaluation, the patient was brought to the Vascular Anomalies Clinic where biopsies of the lesions were deemed the next most appropriate option. Biopsies revealed plexiform neurofibromas. These are pathognomonic for NF type 1. Patient has a full-body MRI scheduled to determine extent of lesions.
Literature searches have noted the MRIs of superficial plexiform neurofibromas can be misread as venolymphatic malformations(O’Keefe). This explains the initial confusion of the original MRI done at 3 years of age. Also contributing to the delay in diagnosis is that during initial presentation at 3 years of age the patient had only one café au lait macule. She did not then meet criteria for NF type 1.
Now that a diagnosis has been rendered more radiologic, and perhaps histopathologic, procedures need to be performed. Friedrich et al. note that when 22 NF type 1 patients were investigated clinically and radiographically, 11 had trigeminal plexiform neurofibromas and 11 had multiple cutaneous neurofibromas. Maxillary sinus malformations were present in those with trigeminal plexiform neurofibromas. Thus, midfacial overgrowth can greatly complicate the care of these patients. It will be important to determine the extent of her facial lesions for cosmesis and to determine if these lesions are starting to compress vital organs.

This case took over 4 years, and multiple specialties, to determine the correct diagnosis of neurofibromatosis type 1. Now that the diagnosis has been determined there is much debate on how to further treat the patient for both functional, as well as cosmetic, reasons. These decisions will be reached after further MRI imaging is performed of the head and neck.

TREATMENT:

Once radiographic studies are performed, is it necessary to have a biopsy performed of her facial lesion? What other diagnostic studies should be performed? What procedures can be entertained to decrease the size of the tumurous masses?

REFERENCES:

1) Paller A. Hurwitz Clinical Pediatric Dermatology. 3rd ed.
2) Spitz J.L. (2005). Genodermatoses: A Clinical Guide to Genetic Disorders. 2nd ed. Philadelphia: Lippincott Williams & Wilkins.
3) Mallory SB, Alanna B, Chern P. Illustrated Manual of Pediatric Dermatology
4) James W.D., Berger T.G., Elston D.M. (2006). Andrew’s Diseases of the Skin, 10th ed. Canada: Elsevier.
5) Tsao, H. (2008). Neurofibromatosis and Tuberous Sclerosis. In Bolognia JL et al. (Ed.) Dermatology, 2nd ed. (pp. 825-832). Spain: Mosby.
6) Garzon MC et al. Vascular Malformations Part II: Associated syndromes. JAAD. Pgs 541-558.
7) Freidrich RE, Giese M, Mautner VF, Schmelzie R, Scheuer HA. Abnormalities of the maxillary sinus in type 1 NF. Mund Kiefer Gesichtschir, 2002 Sep 6(5):363-7.
8) Patil K, Mahima VG, Shetty SK, Lahari K. Facial plexiform neurofibroma in a child with NF 1: a case report. J Indian Soc Pedod Prev Dent. 2007 Mar; 25(1):30-5.
9) O’Keefe P, Reid J, Morrison S, Vidimos A, DiFiore J. Unexpected diagnosis of superficial NF in a lesion with imaging features of a vascular malformation. Pediatr Radiol 2005 Dec; 35(12):1250-3.

Additional Comment:

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